A method for estimating cancer risk in p53 mutation carriers.

Germline mutations of the tumor-suppressor gene p53 have been described in families with multiple neoplasms as Li-Fraumeni syndrome families, or in subjects with second malignant tumor. In order to evaluate the increase in risk of cancer due to these mutations, a family study is being carried out. In families with a proband who developed a cancer before age 16, we select those with at least one cancer before age 45 among first- and second-degree relatives of the proband. All family members are screened for p53 germline mutations if the proband is a carrier of a mutation. We present here a method to estimate the probability that a carrier of a p53 germline mutation develops a given malignant tumor at a given age. This method uses the principle of maximum likelihood estimation. It takes into account the fact that individuals are related within a family, that some of them are not genotyped for p53, and that families have been selected on the criterion of existence of cancer. Simulated data allowed us to validate the method.